Fluorinated compounds and method for preparation



United States Patent 3,232,946 FLUORINATED COMPOUNDS AND METHOD FOR PREPARATION Robert N. Haszeldine, Disley, and Ronald E. Banks,

Manchester, England, and Alfred E. Ginsberg, (literdollendorf, Germany, assignors to Pennsalt Chemicals Corporation, Philadelphia, Pa., a corporation of Pennsylvania No Drawing. Filed Mar. 14, 1961, Ser. No. 95,476 Claims priority, application Great Britain, Mar. 22, 1960, 10,119/60 8 Claims. (Cl. 260--2l0) This invention relates to new perfluorinated heterocyclic carbon compounds and methods for their preparation.

The new compounds of the invention may be described generally as perfluorinated heterocyclic carbon compounds with marked aromatic character having conjugated double bonds and one or more nitrogen atoms as members of the ring. The term perfluorinated as used herein refers to compounds containing only fluorine in addition to carbon and nitrogen atoms. The preferred compounds have one or more six membered rings, at least one of which contains one or more ring nitrogen atoms. From the standpoint of ease of preparation and availability of starting materials, compounds containing a single six membered ring made up of carbon and nitrogen atoms and having one or two nitrogen atoms and three conjugated double bonds, such as pentafluoropyridine, are most preferred. The heterocyclic ring may be substituted or unsubstituted. Thus, it may contain perfluoroalkyl substituent groups such as perfluoromethyl, perfiuoroethyl, perfluoropropyl, etc.

The compounds of the invention may be prepared by defluorination of corresponding more completely saturated perfluorinated N-heterocyclic compounds. The precursor compounds should have at least one ring nitrogen atom carrying fluorine. It is believed that the defluorination is initiated at the nitrogen attached fluorine atom, and that the defluorination reaction, thus initiated, proceeds readily to the removal of the additional fluorine atoms to produce the conjugated ring system characterizing the compounds of the invention.

The preferred starting materials are saturated perfluorinated N-heterocyclics. Such compounds may be prepared readily by electrochemical fluorination of the corresponding heterocyclic compound in the hydrocarbon series, such as by the electrochemical fluorination of pyridine, or of quinoline, or of isoquinoline. Such electrochemical fiuorination procedures, which are described in detail in US. Patent 2,519,983 to Simons, produce saturated, fully fiuorinated compounds in which all hydrogens are replaced by fluorine and in which ring nitrogen atoms are also fluorinated. However, Where available, the precursors for the compounds of the invention may be corresponding perfluorinated N-heterocyclics which contain olefinic unsaturation in the ring provided that at least one of the ring nitrogen atoms carries a fluorine atom.

The defluorination of the precursor compound is carried out by bringing it into contact with a hot metal for a short time at sub-atmospheric pressure. The metal serves as a defluorinating agent and is converted to metal fluoride in the reaction. The preferred metals are iron and nickel, but in general, the transition heavy metals particularly cobalt, manganese, chromium, titanium and copper, as well as certain metals of Group II specifically magnesium and zinc, the the Group III metal aluminum, may be used.

The temperature at which the contacting is carried out should not be less than about 300 C. nor higher than about 900 C., preferred temperatures being in the range of from about 500 to 750 C.

Sub-atmospheric pressures are required to obtain practical yields. In general, the reaction pressure may range from 0.1 to 400 mm. Hg absolute and preferably from 0.1 to about 10 mm. Hg absolute. A convenient operating pressure giving good results in many cases is of the order of l to 2 mm. Hg absolute.

A short reaction or contact time is preferred. At higher temperatures eg from 600 to 700 C., reaction times of the order of seconds ranging e.g. from 0.1 secend to 10 seconds are generally satisfactory, whereas at lower temperatures longer reaction periods may be required ranging e.g. from one up to three or four minutes.

As pointed out above, it is believed that the defluorination is initiated at the nitrogen attached fluorine atom. The nitrogen atom exerts an activating effect on the defluorination since the defiuorination reaction of the invention proceeds in good yields under conditions that do not cause defiuorination of alicyclic perfluoro compounds such as perfluorocyclohexane of perfluoromethyl cyclohexane. indeed, even with much longer contact times and much higher temperatures and pressures than those used in the present invention, alicyclic perfluoro compounds are not defluorinated to form aromatic compounds.

Typical starting materials which may be defluorinated to produce the novel perfluorinated N-heterocyclic aromatic compounds of the invention containing conjugated double bonds include undecafiuoropiperidine which may be defiuorinated to produce pentafluoropyridine in accordance with the following:

Pentafluoropyridine may be also prepared by the defiuorination of an olefinically unsaturated perfluoropiperidine such as A -nonaflu-oropiperidine in accordance with the following:

From heptadecafluoroquinoline, heptafiuoroquinoline is obtained in accordance with the following:

Similarly, from heptadecafluoroisoquinoline there may be obtained heptafiuoroisoquinoline by defiuorination in accordance with the following:

The last two examples represent the application of the invention to compounds containing two six membered rings, the rings in this case being condensed rings.

cordance with the following:

or the defluorination of decafluoropyrimidine to obtain tetrafiuoropyrimidine in accordance with the following:

or the defiuorination of Z-trifiuoromethyldecafiuoropiperidine to obtain Z-trifluoromethyltetraiiuoropyridine in ac- The following examples are intended to illustrate specific modes of carrying out the invention.

Example 1 Undecafluoropiperidine, used as the starting material in this example, is prepared by the electrochemical fiuorination of pyridine in accordance with the general procedure described in U.S. Patent 2,519,983 to Simons. Undecafluoropiperidine is passed through a nickel tube having an internal diameter of 18 millimeters packed tightly with fine iron Wire and heated to 600 C. over a length of 35 centimeters. The tube is maintained at a pressure of 1 mm. Hg absolute and the residence time of the reactant in the heated zone is 1.6 seconds. On collecting the efiiuent from the tube, the products are identified as 68% of a mixture of unchanged perfiuoropiperidine and heterocyclic olefins of the formulae C F N and C F N and 38 weight percent of pentafluoropyridine (greater than 20% yield). Using large scale gas chromatography for the final purification of the pentafiuoropyridine, this is shown to be a colorless liquid having a melting point of -4l.5 C. a boiling point of 83.5 C. and a refractive index 11 1.3856.

Analysis-Calculated for C F N: C, 35.5%; N, 8.3%. Molecular weight 169. Found: C, 35.6%; N, 8.3%. Molecular weight 165. The infrared spectrum of pentafluoropyridine vapor reveals a characteristic vibration near 1497 cm.- indicating that appreciable aromatic character is associated with the ring.

Example 2 Undecafluoropiperidine is passed through a nickel tube packed with iron wire under essentially the same conditions as in Example 1. A 26% yield of pentafiuoropyridine is obtained.

Jtamp e Undecafluoropiperidine is passed through a heated nickel tube packed with iron as in the previous example and under the same conditions except that the temperature is raised at 620 C. Pentafluoropyridine is obtained in a 20% yield.

4 Example 4 Undecafiuoropiperidine is passed through an electrically heated nickel tube 63.5 centimeters long and 19 millimeters in internal diameter, packed with iron wire, and heated to 500 C. over about 35 centimeters of its length. The tube is maintained at a pressure of 221 mm. Hg absolute and the residence time of the reactant in the heated zone is about 4 minutes. This reaction gives mostly a mixture of unsaturated N-heterocyclic compounds of molecular formulae C NF and C NF together with a small amount (about one-tenth percent) of pentafiuoropyridine. This example illustrates the lower yields obtained at higher pressures.

Example 5 Heptadecafluoroquinoline (which may be prepared e.g. as described by Haszeldine and Smith, Journal of Chemical Society (London), 1956, p. 783) is passed through a nickel tube as described in the previous example heated to a temperature of approximately 600 C. and packed with iron wire. The tube is maintained at a pressure of approximately 1 mm. Hg absolute and the residence time of the reactant in the heated zone is approximately 2 seconds. From this reaction there is recovered a good yield of heptafluoroquinoline.

The compounds of the invention, due to their perfiuorinated character are relatively stable and are useful as heat exchange fluids, damping fluids, hydraulic fluids and the like where non-flammability and chemical and heat stability are important factors.

The compounds of the invention are also useful as intermediates for the preparation of fiuorinated analogues of pharmaceutically active materials. Derivatives of the nitrogen heterocyclics such as nicotinic acid and its amide, nicotinamide, have recognized pharmaceutical activity. They are used for the treatment of human pellagra. Nicotinamide is a component of the important diand triphosphopyridine nucleotides, coenzymes I and II. Vitamin B (pyridoxine) is another important pyridine derivative. Other derivatives, e.g. isonicotinic hydrazide, are used in the treatment of tuberculosis. The com pounds of the invention, providing as they do perfiuorinated ring compounds of aromatic character, aiford starting materials for the preparation of fiuorinated analogs of such pharmaceutically important materials which analogs would be expected to possess modified and in some cases improved pharmaceutical activity due to the presence of the fluorine substituents.

We claim:

11. Pentafluoropyridine.

2. A method for the preparation of perfiuorinated N- hetcrocyclic compounds selected from the class consisting of pentafiuoropyridine, heptafiuoroquinoline, heptafluoroisoquinoline,

tetrafiuoropyrazine, tetrafluoropyrimidine and the pertluoroalkyl substituted derivatives of said compounds wherein the perfluoroalkyl group contains from 1 to 3 carbon atoms, said method comprising the step of contacting a corresponding more completely saturated perfluorinated N-heterocyclic starting material in which at least one ring nitrogen atom carries a fluorine atom with a metal selected from the class consisting of iron, nickel, cobalt, manganese, chromium, titanium, copper, magnesium, zinc and aluminum at a temperature of 300 C. to 900 C., at a sub-atmospheric pressure of less than 400 mm. Hg absolute and for a contact time of less than 4 minutes.

3. A method for the preparation of pentafiuoropyridine which comprises contacting undecafiuoropiperidine a metal selected from the class consisting of iron, nickel, cobalt, manganese, chromium, titanium, copper, magnesium, zinc and aluminum at a temperature of from 500 C. to 750 C. at a sub-atmospheric pressure of from 0.1 to 10 mm. Hg absolute and at a contact time of less than 10 seconds.

4. A method in accordance with claim 2 in which said metal is iron.

5. A method in accordance with claim 2 in which said reaction is carried out at sub-atmospheric pressure of from 0.1 to 400 mm. Hg absolute.

6. A method in accordance with claim 2 in which said reaction is carried out at a pressure of from 0.1 to 10 mm. Hg absolute.

7. A method in accordance with claim 2 in which said reaction is carried out at a temperature of from 500 to 750 C.

8. A method in accordance with claim 3 in which said metal is iron.

References Cited by the Examiner UNITED STATES PATENTS 1,886,480 11/1932 Haller et a1. 260-248 2,442,473 6/1948 Sayward et al. 260250 2,937,171 5/1960 Smith 260-248 6 OTHER REFERENCES Bobranski et al.: Ber. Deut. Chem., Vol. 71, p. 2385 (1938).

Burdon et aL: Nature, vol. 186, p. 231 (Apr. 16, 1960).

Gething et al.: Nature, vol. 183, p. 586 (1959).

Gething et aL: Nature, vol. 183, p. 588 (1959).

Haszeldine: J. Chem. Soc., 1950, pp. 1638, 1966.

Haszeldine: J. Chem. Soc., 1951, p. 102.

Klemm: Inorganic Chemistry, volume 1, pages 239 Klingsberg: Pyridine and Its Deriv., Part 2, pp. 302- 385, 389 (1961).

Schroeder: Iourn. of Am. Chem. Soc., volume 82, page 4115 (August 1960).

WALTER A. MODANCE, Primary Examiner.

IRVING MARCUS, Examiner. 

2. A METHOD FOR THE PREPARATION OF PERFLUORINATED NHETEROCYCLIC COMPOUNDS SELECTED FROM THE CLASS CONSISTING OF PENTAFLUOROPYRIDINE, HEPTAFLUOROQUINOLINE, HEPTAFLUOROISOQUINOLINE, TETRAFLUOROPYRAZINE, TETRAFLUOROPYRIMIDINE AND THE PERFLUOROALKYL SUBSTITUTED DERIVATIVES OF SAID COMPOUNDS WHEREIN THE PERFLUOROALKYL GROUP CONTAINS FROM 1 TO 3 CARBON ATOMS, SAID METHOD COMPRISING THE STEP OF CONTACTING A CORRESPONDING MORE COMPLETELY SATURATED PERFLUORINATED N-HETEROCYCLIC STARTING MATERIAL IN WHICH AT LEAST ONE RING NITROGEN ATOM CARRIES A FLUORINE ATOM WITH A METAL SELECTED FROM THE CLASS CONSISTING OF IRON, NICKEL, COBALT, MANGANESE, CHROMIUM, TITANIUM, COPPER, MAGNESIUM, ZINC AND ALUMINUM AT A TEMPERATURE OF 300* C. TO 900*C., AT A SUB-ATMOSPHERIC PRESSURE OF LESS THAN 400 MM. HG ABSOLUTE AND FOR A CONTACT TIME OF LESS THAN 4 MINUTES. 